Antonova, Alexandra Sergeevna

Antonova Alexandra S., Zubkov Fedor I.

Catalytic olefin metathesis using Hoveyda-Grubbs type ruthenium complexes is a powerful tool for creating complex molecules possessing a variety of practically useful properties. This method is also applied for obtaining modern polymer materials from low-demand petroleum products. Among all ruthenium complexes containing five- or six-membered chelate rings, the commercially available HG-II catalyst is the most common. In addition, other Hoveyda-Grubbs type complexes, which include a Het→Ru donor–acceptor bond in the chelate ring, often exhibit metathesis activity equal to or superior to that of HG-II. This review considers second-generation N-heterocyclic ruthenium carbene Hoveyda-Grubbs type complexes with donor–acceptor bonds such as O→Ru, S→Ru, Se→Ru, N→Ru, P→Ru and Hal→Ru in the chelate ring. Methods of preparation, analysis of stability and catalytic activity of such complexes are compared, and examples of the application of these organometallic ruthenium derivatives in the synthesis of practically relevant products are provided. The literature from 2010 to 2023 is summarized, making this review useful for a broad audience of chemists working in heterocyclic and organometallic chemistry, as well as practitioners involved in the production of catalysts and polymers.The bibliography includes 174 references.

Mammadova G.Z., Atioğlu Z., Akkurt M., Grigoriev M.S., Volchkov N.S., Azizova A.N., Bhattarai A., Antonova A.S.

The title compound, [RuCl2(C33H43N3O)], is an example of a new generation of N,N-dialkyl ruthenium catalysts with an N—Ru coordination bond as part of a six-membered chelate ring. The Ru atom has an Addison τ parameter of 0.244, which indicates a geometry intermediate between square-based pyramidal and trigonal–bipyramidal. The complex shows the usual trans arrangement of the two chlorides, with Ru—Cl bond lengths of 2.3515 (8) and 2.379 (7) Å, and a Cl—Ru—Cl angle of 158.02 (3)°. One of the chlorine atoms and the atoms of the 2-methoxy-N-methyl-N-[(2-methylphenyl)methyl]ethane-1-amine group of the title complex display disorder over two positions in a 0.889 (2): 0.111 (2) ratio.

Kumandin P.A., Antonova A.S., Novikov R.A., Vasilyev K.A., Vinokurova M.A., Grigoriev M.S., Novikov A.P., Polianskaia D.K., Polyanskii K.B., Zubkov F.I.

This work continues our group’s research into the synthesis and study of the catalytic activity of ruthenium chelates with various heteroatoms (O, S, N, and Se) in a six-membered ring. It was found that second-generation Hoveyda–Grubbs-type catalysts containing a sulfur-ruthenium coordinate bond in a six-membered chelate ring can be prepared easily and in high yields using standard procedures, based on the interaction between (2-vinylbenzyl)sulfanes and Ind II (the common precursor for Ru-complex synthesis). The obtained ruthenium derivatives, with a donor-acceptor S → Ru bond, can exist in two isomeric forms according to the arrangement of substituents around the central metal atom. Kinetically controlled trans-isomers are formed at temperatures below 80 °C in heptane and are less thermodynamically stable compared with cis-isomers, which arise under heating of trans-S-chelates in 1,2-dichloroethane at 110 °C. The structures of all the cis- and trans-isomers were determined and characterized in detail by X-ray diffraction and nuclear magnetic resonance. The study of the activity of the catalysts in standard ring-closing metathesis and ring-opening metathesis polymerization reactions showed that the cis-isomers are inactive in the absence of thermal or UV activation, while trans-complexes of the same type display excellent catalytic properties at r.t. that are superior to those of the commercially available HG-II catalyst. The structure, spectral characteristics, and catalytic activity of the catalysts containing an S → Ru bond in a six-membered chelate ring were compared with their five-membered analogues obtained in previous works.

Vasilyev K.A., Antonova A.S., Volchkov N.S., Logvinenko N.A., Nikitina E.V., Grigoriev M.S., Novikov A.P., Kouznetsov V.V., Polyanskii K.B., Zubkov F.I.

An efficient approach to the synthesis of olefin metathesis HG-type catalysts containing an N→Ru bond in a six-membered chelate ring was proposed. For the most part, these ruthenium chelates can be prepared easily and in high yields based on the interaction between 2-vinylbenzylamines and Ind II (the common precursor for Ru-complex synthesis). It was demonstrated that the increase of the steric volume of substituents attached to the nitrogen atom and in the α-position of the benzylidene fragment leads to a dramatic decrease in the stability of the target ruthenium complexes. The bulkiest iPr substituent bonded to the nitrogen atom or to the α-position does not allow the closing of the chelate cycle. N,N-Diethyl-1-(2-vinylphenyl)propan-1-amine is a limiting case; its interaction with Ind II makes it possible to isolate the corresponding ruthenium chelate in a low yield (5%). Catalytic activity of the synthesized complexes was tested in RCM reactions and compared with α-unsubstituted catalysts obtained previously. The structural peculiarities of the final ruthenium complexes were thoroughly investigated using XRD and NMR analysis, which allowed making a reliable correlation between the structure of the complexes and their catalytic properties.

Antonova A.S., Nikitina E.V., Valchuk K.S., Grigoriev M.S., Gomila R.M., Frontera A., Zubkov F.I.

The existence of a “through-space” alpha-effect is analyzed in all-cis 3a,6 : 4,5 : 7,9a-triepoxy and 3a,6 : 7,9a-diepoxybenzo[de]isoquinolines. It is demonstrated that the H-bonds are enhanced by the α-effect.

Goryainov S.V., Esparza C., Kulikova L.N., Borisova A.R., Kumandin P.A., Antonova A.S., Rystsova E.O., Oshakbaev M.T., Omarova G.T., Polovkov N.Y.

We recorded and interpreted DART mass spectra of Hoveyda–Grubbs catalysts with N→Ru and S→Ru coordination bonds. The set of ions formed under DART ionization conditions is similar to those obtained using matrix-assisted laser desorption/ionization mass spectrometry. The optimal conditions (ionization gas, gas flow temperature) for recording DART mass spectra of the studied compounds were determined.

Yarovaya O.I., Kovaleva K.S., Zaykovskaya A.A., Yashina L.N., Scherbakova N.S., Scherbakov D.N., Borisevich S.S., Zubkov F.I., Antonova A.S., Peshkov R.Y., Eltsov I.V., Pyankov O.V., Maksyutov R.A., Salakhutdinov N.F.

This work presents the design and synthesis of camphor, fenchone, and norcamphor N -acylhydrazone derivatives as a new class of inhibitors of the Hantaan virus, which causes haemorrhagic fever with renal syndrome (HFRS). A cytopathic model was developed for testing chemotherapeutics against the Hantaan virus, strain 76–118. In addition, a study of the antiviral activity was carried out using a pseudoviral system. It was found that the hit compound possesses significant activity (IC 50 = 7.6 ± 2 µM) along with low toxicity (CC 50 > 1000 µM). Using molecular docking procedures, the binding with Hantavirus nucleoprotein was evaluated and the correlation between the structure of the synthesised compounds and the antiviral activity was established.

Kumandin P.A., Antonova A.S., Alekseeva K.A., Nikitina E.V., Novikov R.A., Vasilyev K.A., Sinelshchikova A.A., Grigoriev M.S., Polyanskii K.B., Zubkov F.I.

An efficient approach to the synthesis of new types of Hoveyda–Grubbs catalysts containing an N→Ru bond in a six-membered chelate ring is proposed. The synthesis of the organometallic compounds is based on the interaction of ready accessible 2-vinylbenzylamines and 1,3-bis(2,4,6-trimethylphenyl)-2-trichloromethylimidazolidine ligands with dichloro(3-phenyl-1H-inden-1-ylidene)bis(tricyclohexylphosphane)ruthenate, and it afforded the target ruthenium complexes in 70–80% yields. Areas of practical utility and potential applications of the obtained chelates were highlighted by tests of the catalysts in different olefin cross-metathesis (CM) and ring-closing-metathesis (RCM) reactions. These experiments revealed a high catalytic performance (up to 10–2 mol %) of all the synthesized structures in a broad temperature range. The structural peculiarities of the resultant ruthenium catalysts were thoroughly investigated by X-ray crystallography, which allowed making a reliable correlation between the structure of the metallo-complexes and their catalytic properties. It was proved that the bond length between ruthenium and nitrogen in the six-membered chelate ring has the greatest effect on the stability and efficiency of the catalyst. As a rule, the shorter and stronger the N→Ru bond, the higher the stability of the complex and the worse its catalytic characteristics. In turn, the coordination N→Ru bond length can be finely tuned and varied over a wide range of values by changing the steric volume of the cyclic substituents at the nitrogen atom, which will make it possible, as appropriate, to obtain in the future metal complexes with predictable stability and the required catalytic activity. Also, it was found that complexes in which the nitrogen atom is included in the morpholine or isoquinoline rings are the most efficient catalysts in this series. An attempt to establish a correlation between the N→Ru bond length and the 1H and 13C chemical shifts in the Ru═CH fragment has been made.

Antonova A.S., Vinokurova M.A., Kumandin P.A., Merkulova N.L., Sinelshchikova A.A., Grigoriev M.S., Novikov R.A., Kouznetsov V.V., Polyanskii K.B., Zubkov F.I.

The ring rearrangement metathesis (RRM) of a trans-cis diastereomer mixture of methyl 3-allyl-3a,6-epoxyisoindole-7-carboxylates derived from cheap, accessible and renewable furan-based precursors in the presence of a new class of Hoveyda–Grubbs-type catalysts, comprising an N→Ru coordinate bond in a six-membered ring, results in the difficult-to-obtain natural product-like cyclopenta[b]furo[2,3-c]pyrroles. In this process, only one diastereomer with a trans-arrangement of the 3-allyl fragment relative to the 3a,6-epoxy bridge enters into the rearrangement, while the cis-isomers polymerize almost completely under the same conditions. The tested catalysts are active in the temperature range from 60 to 120 °C at a concentration of 0.5 mol % and provide better yields of the target tricycles compared to the most popular commercially available second-generation Hoveyda–Grubbs catalyst. The diastereoselectivity of the intramolecular Diels–Alder reaction furan (IMDAF) reaction between starting 1-(furan-2-yl)but-3-en-1-amines and maleic anhydride, leading to 3a,6-epoxyisoindole-7-carboxylates, was studied as well.

Laev Sergey Sergeevich, Yarovaya Olga I., Salakhutdinov Nariman F.

This review is devoted to small molecules (compounds with molecular weights of up to 800–900 Da) that show activity against viruses causing hemorrhagic fevers that occur in Russia. The review presents compounds of various chemical classes that have shown antiviral effect against the causative agents of three acute infectious diseases, Omsk hemorrhagic fever, Crimean-Congo hemorrhagic fever, and hemorrhagic fever with renal syndrome, or alleviate symptoms of these diseases. Despite the severity and high prevalence of hemorrhagic fevers, it should be noted that there are no effective medications for the prevention and treatment of hemorrhagic fevers in Russia and that the search for new antiviral agents is highly relevant. The synthetic nucleoside ribavirin is commonly used for the treatment, but it is not sufficiently effective. The structures and activity parameters (half maximal inhibitory concentration) of the indicated compounds are given and putative mechanisms of their action are discussed. The review summarizes the data published over the whole period of studies of these diseases.The bibliography includes 160 references.

Ibragimova U.M., Valuisky N.V., Sorokina S.A., Zhukova X.I., Raiberg V.R., Litvinov R.A.

Abstract—The extracellular matrix (ECM) provides structural support and regulates cell activity. ECM dysfunction due to metabolic pathologies or aging can lead to disease. Developing ECM protectors is crucial for the etiological prevention and treatment of pathologies associated with ECM alterations. Key mechanisms of pathological changes in the ECM include nonenzymatic reactions, such as glycation and glycoxidation. The potential of agents as ECM protectors can be assessed by their capability of inhibiting these processes. Compounds based on heterocyclic scaffolds with partially hydrogenated isoindole fragments were tested for capability of slowing down the formation of advanced glycation end-products (AGEs). A combination of in silico and in vitro approaches was employed. In the in silico study, the energies of the frontier molecular orbitals of the compounds were determined using the ab initio method with the 6-311G(d,p) basis set. Antiglycation activity was then investigated in the glycation reaction of bovine serum albumin (BSA) with glucose, using BSA as a model protein. Pyridoxamine served as a reference compound. Antiglycation activities of the compounds were evaluated spectrofluorometrically by measuring the fluorescent products at excitation/emission wavelengths of 440/520 nm, which are not typically used for assessing antiglycation properties., Glycation and oxidation products in the human skin can be detected at these wavelengths. Their amount correlates with chronological age, in contrast to certain other glycation products. It was found experimentally that the energies of the frontier molecular orbitals of the compounds can serve as predictors of their capability of slowing down the formation of fluorescent products detected at 440/520 nm. Inhibiting the formation of the products may be significant for treatment and prevention of diseases, including metabolic, fibrotic, or age-associated conditions. At 100 µM, series of hydrogenated 3a,6-epoxyisoindole-7-carboxylic acids (compounds of type XIII) and cyclopenta[b]furo[2,3-c]pyrrole-3-carboxylic acids (structures of type XIX) were found to display the most pronounced antiglycation properties.

Kinugawa T., Mitsusada S., Orito N., Matsuo T.

Obydennov D., Viktorova V.V., Kovaleva K.S., Yarovaya O.I., Khasanov S.A., Bormotov N.I., Esaulkova I.L., Serova O.A., Zarubaev V.V., Shishkina L.N., Salakhutdinov N.F., Sosnovskikh V.Y.

AbstractSelective synthesis of polycarbonyl conjugates of (+)‐fenchone and (+)‐camphor was carried out (44–91 % yields) via the ring‐opening transformation of 5‐acyl‐4‐pyrones with hydrazones of the corresponding monoterpenoids. A strong influence of the hydrazone fragment on the observed tautomeric equilibrium of the tricarbonyl system was shown. Although the major tautomer of the conjugates is the acyclic polycarbonyl form, the camphor‐based conjugates undergo new type of ring‐chain tautomerism, diketoenaminone‐dihydropyridone equilibrium, and predominantly exist in the cyclic dihydropyridone form in DMSO‐d6. The polyketones can undergo intramolecular cyclization to form N‐amino‐4‐pyridones in high selectivity. In vitro screening for activity against the influenza virus H1 N1 and vaccinia virus was estimated for the obtained conjugates. The (+)‐fenchone derivatives demonstrated the higher activity against vaccinia virus than camphor derivatives. The conjugate, which was prepared from diethyl isochelidonate and hydrazone (+)‐fenchone, showed the highest activity against vaccinia virus (SI=17).

Medley A.W., Patel D., Utne C., Bender T.A.

Akhmetov A.R., Tulyabaev A.R., Sabirov D.S.

Zazza C., Sanna N., Borocci S., Grandinetti F.

AbstractThe recent discovery that metallophilic interactions between cyclometalated palladium supramolecular nanostructures – with efficient tumour accumulation rate in a skin melanoma model – maintain excellent photodynamic properties even in a hypoxic microenvironment has inspired the present study focused on the theoretical predictions of optical properties of the bis‐cyclometalated palladium compound in different contexts. More specifically, structural and UV/Vis absorption properties of both monomeric and dimeric forms of this anticancer drug are well reproduced with a Time‐Dependent Density Functional Theoretical (TD‐DFT) approach based on Exchange–Correlation (XC) hybrid functionals in conjunction with conductor‐like and polarization solvation effects. A further novelty is represented by a fine investigation of the supramolecular interactions between the different subunits of the drug via dispersion force correction and Quantum Theory of Atoms in Molecules (QTAIM). This contribution while supporting the photoexcitation properties derived in laboratory following the self‐assembly of monomeric units when passing from dimethyl sulfoxide (DMSO) to a H2O/DMSO mixture at 298 K, shed some light on the nature of the chemical interactions modulating the formation of nano‐size aggregates.

Antonova Alexandra S., Zubkov Fedor I.

Catalytic olefin metathesis using Hoveyda-Grubbs type ruthenium complexes is a powerful tool for creating complex molecules possessing a variety of practically useful properties. This method is also applied for obtaining modern polymer materials from low-demand petroleum products. Among all ruthenium complexes containing five- or six-membered chelate rings, the commercially available HG-II catalyst is the most common. In addition, other Hoveyda-Grubbs type complexes, which include a Het→Ru donor–acceptor bond in the chelate ring, often exhibit metathesis activity equal to or superior to that of HG-II. This review considers second-generation N-heterocyclic ruthenium carbene Hoveyda-Grubbs type complexes with donor–acceptor bonds such as O→Ru, S→Ru, Se→Ru, N→Ru, P→Ru and Hal→Ru in the chelate ring. Methods of preparation, analysis of stability and catalytic activity of such complexes are compared, and examples of the application of these organometallic ruthenium derivatives in the synthesis of practically relevant products are provided. The literature from 2010 to 2023 is summarized, making this review useful for a broad audience of chemists working in heterocyclic and organometallic chemistry, as well as practitioners involved in the production of catalysts and polymers.The bibliography includes 174 references.

Charushin Valery N., Verbitskiy Egor V., Chupakhin Oleg N., Vorobyeva Daria V., Gribanov Pavel S., Osipov Sergey N., Ivanov Andrey V., Martynovskaya Svetlana V., Sagitova Elena F., Dyachenko Vladimir D., Dyachenko Ivan V., Krivokolysko Sergey G., Dotsenko Viktor V., Aksenov Aleksandr V., Aksenov Dmitrii A., et. al.

The chemistry of heterocyclic compounds has traditionally been and remains a bright area of chemical science in Russia. This is due to the fact that many heterocycles find the widest application. These compounds are the key structural fragments of most drugs, plant protection agents. Many natural compounds are also derivatives of heterocycles. At present, more than half of the hundreds of millions of known chemical compounds are heterocycles. This collective review is devoted to the achievements of Russian chemists in this field over the last 15–20 years. The review presents the achievements of leading heterocyclists representing both RAS institutes and university science. It is worth noting the wide scope of the review, both in terms of the geography of author teams, covering the whole of our large country, and in terms of the diversity of research areas. Practically all major types of heterocycles are represented in the review. The special attention is focused on the practical applications of heterocycles in the design of new drugs and biologically active compounds, high-energy molecules, materials for organic electronics and photovoltaics, new ligands for coordination chemistry, and many other rapidly developing areas. These practical advances would not be possible without the development of new fundamental transformations in heterocyclic chemistry.The bibliography includes 2237 references.

Galla R., Murthi V.R., Shaik Y., Karnati S., Vankadoth U.N., Amineni U.

Since 2019, the SARS-CoV-2 infection has continued to cause significant human suffering. Numerous investigations into the viral pathogenesis have led to converging conclusions on how the virus enters and spreads within the host. The main protease (Mpro) of coronaviruses has been considered as an attractive therapeutic target because of its important role in processing polyproteins translated from viral RNA. Many studies discovered that phytoconstituents possess potent antiviral activities. Hence, in the present work, 439 co-crystal ligands of SARS-CoV-2 Mpro were collected and docked with Mpro of SARS-CoV-2 (PDB ID:7AEH) to identify best crystal ligand. Among all the crystal ligands collected, HF0 (7-O-methyl-dihydromyricetin) showed good XP G score -7.872 Kcal/Mol and it was selected as reference to compare the docking scores of phytoconstituents. Then, molecular docking study was performed for 274 antiviral phytoconstituents from various medicinal plants against Mpro of SARS-CoV-2. Molecular docking studies found that seven phytoconstituents exhibited better docking scores than best co-crystal ligand HF0. Among the seven best docked phytoconstituents, 3,4-dicaffeoylquinic acid showed good interactions with key amino acid residues in substrate binding site of Mpro with XPG Score –9.721 Kcal/Mol. Qikprop results indicated that the most phytoconstituents have demonstrated favourable pharmacological characteristics. Interaction fingerprint analysis revealed that all the seven best docked phytoconstituents of the present study bound to Glu166, key residue situated in the centre of the substrate binding site of Mpro resulting in the reduction of the catalytic activity of main protease thus blocking the replication of SARS-CoV-2.

Yıldırım A.

Tandem Diels–Alder reactions are often used for the straightforward formation of complex natural compounds and the fused polycyclic systems contained in their precursors. In the second step of this reaction, regio- and stereochemically controlled intramolecular cyclization leads to the formation of versatile nitrogen-containing tricyclic systems. However, these useful organic transformations are usually carried out in highly toxic organic solvents such as benzene, toluene, chloroform, etc. Despite recent efforts by 'green chemists', synthetic chemists still use these traditional toxic organic solvents in many of their reactions, even though safer alternatives are available. However, in addition to the harmful effects of these petrochemical solvents on the environment, the prediction that their resources will run out in the near future has led 'green chemists' to explore solvents that can be derived from renewable resources and used effectively in various organic transformations. In this context, we have shown for the first time that the 100% atom-economical tandem Diels–Alder reaction between aminofuranes and maleic anhydride can be carried out successfully in vegetable oils and waxes. The reaction was successfully carried out in sunflower seed oil, olive oil, oleic acid and lauryl myristate under mild reaction conditions. A series of epoxyisoindole-7-carboxylic acid and bisepoxyisoindole-7-carboxylic acids were obtained in good yields after a practical isolation procedure. The results obtained in this study demonstrate the potential of vegetable oils and their renewable materials to provide a reaction medium that is more sustainable than conventional organic solvents in cascade Diels–Alder reactions and can be used repeatedly without significant degradation. These materials also allow the reaction to be completed in less time, with less energy consumption and higher yields.

Wang R., Kong L., Zong X., Zhang M., Chen W., Liu Y., Ma L., Zhao Y.

An interesting diazenylation reaction is demonstrated, which enables the efficient synthesis of hydrazones using active methyne compounds and arylazo sulfones.

Cheng-Sánchez I., Moya-Utrera F., Sarabia F.

Yarovaya O.I., Baev D.S., Kovaleva K.S., Gatilov Y.V., Meshkova Y.V., Marinina M.K., Oreshko V.V., Tolstikova T.G., Salakhutdinov N.F.

Conjugates of isatin and hydrazones based on (+)-camphor and (–)-fenchone were synthesized for the first time. The physicochemical properties of the synthesized compounds have been studied, and for the hydrazone product of fenchone and isatin X-ray diffraction data have been obtained. Molecular modeling of the possible interaction of new compounds with the active site of the basic protease 3CLpro of the SARS-CoV-2 virus was carried out, and the properties of isatin-terpene compounds as inhibitors of the 3CLpro protease were studied. It was found that the new conjugates do not exhibit inhibitory properties against 3CLpro, which makes it possible to clarify the direction of further chemical modifications of monoterpenoid derivatives in order to obtain molecules with antiviral properties.

Mammadova G.Z., Atioğlu Z., Akkurt M., Grigoriev M.S., Volchkov N.S., Azizova A.N., Bhattarai A., Antonova A.S.

The title compound, [RuCl2(C33H43N3O)], is an example of a new generation of N,N-dialkyl ruthenium catalysts with an N—Ru coordination bond as part of a six-membered chelate ring. The Ru atom has an Addison τ parameter of 0.244, which indicates a geometry intermediate between square-based pyramidal and trigonal–bipyramidal. The complex shows the usual trans arrangement of the two chlorides, with Ru—Cl bond lengths of 2.3515 (8) and 2.379 (7) Å, and a Cl—Ru—Cl angle of 158.02 (3)°. One of the chlorine atoms and the atoms of the 2-methoxy-N-methyl-N-[(2-methylphenyl)methyl]ethane-1-amine group of the title complex display disorder over two positions in a 0.889 (2): 0.111 (2) ratio.

Pecak J., Talmazan R.A., Svatunek D., Kirchner K., Podewitz M.

Enríquez‐Figueroa R.A., Pineda‐Contreras A., Vázquez‐Vuelvas O.F., González‐González J., Fomine S.

AbstractDehydrohalogenation of 1,4‐dihalobenzenes and 1,2,4‐trichlorobenzene is performed using n‐BuLi to form benzynes. These benzynes are used as dienophiles in a Diels–Alder reaction with the dienes furan and 2,5‐dimethylfuran to prepare new benzonorbornadiene derivatives. The cycloadducts of furan are polymerized by a ring‐opening metathesis reaction using a Hoveyda–Grubbs ruthenium catalyst. The polymers are characterized by 1H NMR (nuclear magnetic resonance), and unambiguous proton chemical shift assignments are based on the multiplicity pattern of proton resonances. This is confirmed by 2D NMR data from HSQC(Heteronuclear Single Quantum Coherence) and COSY (Correlation Spectroscopy) spectra. The polybenzonorbornadienes have both cis and trans conformation in their chemical structure. The trans conformation is qualitatively in greater proportion observed at 1H NMR experiments. These materials may have syndiotactic microstructure by the lack of correlations in COSY.

Deng M., Wilde M., Welch J.T.

Kinugawa T., Matsuo T.

For regulating olefin metathesis (OM) activities of Hoveyda–Grubbs second-generation complex (HG-II), the structural modification of the benzylidene ligand is a useful strategy. This paper reports the effect of a chalcogen...

Gobbo A., Ma X., Ciancaleoni G., Zacchini S., Biancalana L., Guelfi M., Pampaloni G., Nolan S.P., Marchetti F.

AbstractWhile ruthenium(II) arene complexes have been widely investigated for their potential in catalytic transfer hydrogenation, studies on homologous compounds replacing the arene ligand with the six‐electron donor tris(1‐pyrazolyl)methane (tpm) are almost absent in the literature. The reactions of [RuCl(κ3‐tpm)(PPh3)2]Cl, 1, with a series of nitrogen ligands (L) proceeded with selective PPh3 mono‐substitution, affording the novel complexes [RuCl(κ3‐tpm)(PPh3)(L)]Cl (L=NCMe, 2; NCPh, 3; imidazole, 4) in almost quantitative yields. Products 2–4 were fully characterized by IR and multinuclear NMR spectroscopy, moreover the molecular structure of 4 was ascertained by single crystal X‐ray diffraction. Compounds 2–4 were evaluated as catalytic precursors in the transfer hydrogenation of a series of ketones with isopropanol as the hydrogen source, and 2 exhibited the highest activity. Extensive NMR experiments and DFT calculations allowed to elucidate the mechanism of the transfer hydrogenation process, suggesting the crucial role played by the tpm ligand, reversibly switching from tri‐ to bidentate coordination during the catalytic cycle.

Segalovich-Gerendash G., Baranov M., Lemcoff N.G., Phatake R.S.

Mahmudov K.T., Pombeiro A.J.

Aeissen E., von Seggern A.R., Schmidtmann M., Christoffers J.

Zehnder T.E., Nasrallah D.J., Stanley J.L., Kiernicki J.J., Szymczak N.K., Schindler C.S.

Kumandin P.A., Antonova A.S., Novikov R.A., Vasilyev K.A., Vinokurova M.A., Grigoriev M.S., Novikov A.P., Polianskaia D.K., Polyanskii K.B., Zubkov F.I.

This work continues our group’s research into the synthesis and study of the catalytic activity of ruthenium chelates with various heteroatoms (O, S, N, and Se) in a six-membered ring. It was found that second-generation Hoveyda–Grubbs-type catalysts containing a sulfur-ruthenium coordinate bond in a six-membered chelate ring can be prepared easily and in high yields using standard procedures, based on the interaction between (2-vinylbenzyl)sulfanes and Ind II (the common precursor for Ru-complex synthesis). The obtained ruthenium derivatives, with a donor-acceptor S → Ru bond, can exist in two isomeric forms according to the arrangement of substituents around the central metal atom. Kinetically controlled trans-isomers are formed at temperatures below 80 °C in heptane and are less thermodynamically stable compared with cis-isomers, which arise under heating of trans-S-chelates in 1,2-dichloroethane at 110 °C. The structures of all the cis- and trans-isomers were determined and characterized in detail by X-ray diffraction and nuclear magnetic resonance. The study of the activity of the catalysts in standard ring-closing metathesis and ring-opening metathesis polymerization reactions showed that the cis-isomers are inactive in the absence of thermal or UV activation, while trans-complexes of the same type display excellent catalytic properties at r.t. that are superior to those of the commercially available HG-II catalyst. The structure, spectral characteristics, and catalytic activity of the catalysts containing an S → Ru bond in a six-membered chelate ring were compared with their five-membered analogues obtained in previous works.

Vasilyev K.A., Antonova A.S., Volchkov N.S., Logvinenko N.A., Nikitina E.V., Grigoriev M.S., Novikov A.P., Kouznetsov V.V., Polyanskii K.B., Zubkov F.I.

An efficient approach to the synthesis of olefin metathesis HG-type catalysts containing an N→Ru bond in a six-membered chelate ring was proposed. For the most part, these ruthenium chelates can be prepared easily and in high yields based on the interaction between 2-vinylbenzylamines and Ind II (the common precursor for Ru-complex synthesis). It was demonstrated that the increase of the steric volume of substituents attached to the nitrogen atom and in the α-position of the benzylidene fragment leads to a dramatic decrease in the stability of the target ruthenium complexes. The bulkiest iPr substituent bonded to the nitrogen atom or to the α-position does not allow the closing of the chelate cycle. N,N-Diethyl-1-(2-vinylphenyl)propan-1-amine is a limiting case; its interaction with Ind II makes it possible to isolate the corresponding ruthenium chelate in a low yield (5%). Catalytic activity of the synthesized complexes was tested in RCM reactions and compared with α-unsubstituted catalysts obtained previously. The structural peculiarities of the final ruthenium complexes were thoroughly investigated using XRD and NMR analysis, which allowed making a reliable correlation between the structure of the complexes and their catalytic properties.

Zachmann R.J., Yahata K., Holzheimer M., Jarret M., Wirtz C., Fürstner A.

The dinoflagellate-derived polyether prorocentin is a co-metabolite of the archetypical serine/threonine phosphatase inhibitor okadaic acid. Whereas a structural relationship cannot be missed and a biosynthetic link was proposed, it is currently unknown whether there is any parallel in the bioactivity profile of these natural products. However, it was insinuated in the past that the structure assigned to prorocentin might need to be revised. Indeed, re-examination of the published spectra cast doubts as to the constitution of the fused/spirotricyclic BCD-ring system in the core. To clarify this issue, a flexible synthesis blueprint was devised that allowed us to obtain the originally proposed structure as well as the most plausible amended structure. The key to success was late-stage gold-catalyzed spirocyclization reactions that furnished the isomeric central segments with excellent selectivity. The lexicon of catalytic transformations used to make the required cyclization precursors comprised a titanium-mediated ester methylenation/metathesis cascade, a rare example of a gold-catalyzed allylic substitution, and chain extensions via organocatalytic asymmetric aldehyde propargylation. A wing sector to be attached to the isomeric cores was obtained by Krische allylation, followed by a superbly selective cobalt-catalyzed oxidative cyclization of the resulting di-unsaturated alcohol with the formation of a 2,5-trans-disubstituted tetrahydrofuran; the remaining terminal alkene was elaborated into an appropriate handle for fragment coupling by platinum-catalyzed asymmetric diboration/oxidation. The assembly of the different building blocks to the envisaged isomeric target compounds proved that the structure of prorocentin needs to be revised as disclosed herein.

Jawiczuk M., Kuźmierkiewicz N., Nowacka A.M., Moreń M., Trzaskowski B.

Kovács E., Balterer B., Anh Duc N., Szarka G., Owen M.C., Domján A., Iván B.

A tremendous number of solvents, either as liquids or vapors, contaminate the environment on a daily basis worldwide. Olefin metathesis, which has been widely used as high-yielding protocols for ring-opening metathesis polymerization (ROMP), ring-closing metathesis (RCM), and isomerization reactions, is typically performed in toxic and volatile solvents such as dichloromethane. In this study, the results of our systematic experiments with the Grubbs G1, G2, and Hoveyda-Grubbs HG2 catalysts proved that benzotrifluoride (BTF) can replace dichloromethane (DCM) in these reactions, providing high yields and similar or even higher reaction rates in certain cases. The ROMP of norbornene resulted not only in high yields but also in polynorbornenes with a high molecular weight at low catalyst loadings. Ring-closing metathesis (RCM) experiments proved that, with the exception of the G1 catalyst, RCM occurs with similar high efficiencies in BTF as in DCM. It was found that isomerization of (Z)-but-2-ene-1,4-diyl diacetate with the G2 and HG2 catalysts proceeds at significantly higher initial rates in BTF than in DCM, leading to rapid isomerization with high yields in a short time. Overall, BTF is a suitable solvent for olefin metathesis, such as polymer syntheses by ROMP and the ring-closing and isomerization reactions.

Szczepanik P.M., Mikhaylov A.A., Hylse O., Kučera R., Daďová P., Nečas M., Kubala L., Paruch K., Švenda J.

We report a new synthetic strategy for the flexible preparation of forskolin-like molecules. The approach is different from the previously published works and employs a convergent assembly of the tricyclic labdane-type core from pre-functionalized cyclic building blocks. Stereoselective Michael addition enabled the fragment coupling with excellent control over three newly created contiguous stereocenters, all-carbon quaternary centers included. Silyl enol ether-promoted ring-opening metathesis paired with ring closure were the other key steps enabling concise assembly of the tricyclic core. Late-stage functionalization sequences transformed the tricyclic intermediates into a set of different forskolin-like molecules. The modular nature of the synthetic scheme described herein has the potential to become a general platform for the preparation of analogs of forskolin and other complex tricyclic labdanes.